Surgical repairs number around 800,000 annually in the US alone for ligaments and tendons of the foot and ankle (for example, Achilles tendon), shoulder (for example, rotator cuff), and knee (for example, anterior cruciate ligament), yet the current standards of care involving the implantation of replacement and supporting elements are generally considered by medical practitioners to be less than optimal.
Leading ligament and tendon repair graft products intended to provide biocompatible soft tissue support scaffolds often involve two decades old technologies that in some instance rely on cadaveric tissue or invasive autografting. Allografts are supply-limited, promote scar formation, may provoke an immune response, and have poorly defined turnover rates, all of which inhibit healing. Autografting also extends surgery time and associated trauma, and often adds a second costly procedure to recover the autologous tissue.
For example, the GRAFTJACKET® Regenerative Tissue Matrix is a sheet-like product formed from donated allograft human dermis, aseptically processed to remove cells and then freeze-dried, http://www.wright.com/footandankleproducts/graftjacket. ArthroFLEX® Decellularized Dermal Allograft is a similar acellular dermal extracellular matrix, https://www.arthrex.com/orthobiologics/arthroflex.
Various other approaches have been taken to develop synthetic or semi-synthetic components for implantable devices useful as scaffolds to facilitate repair of, or to support or replace damaged soft tissues such as tendons and ligaments. Such products must function in a variety of challenging biomechanical environments in which multiple functional parameters must be addressed, among them, for example, are compatibility, strength, flexibility and biodegradability.
Among such approaches and products are those disclosed, for example, by Ratcliffe et al., U.S. Pat. No. 9,597,430 (2017), entitled “Synthetic Structure for Soft Tissue Repair”. This patent describes various synthetic fibrillar structures, such as a woven mesh and single or multilayer planar fibrillar forms. According to Ratcliffe, these structures can be made from any biocompatible polymer material capable of providing suitable mechanical properties, bioabsorbable or not. Collagen and lactide are mentioned as suitable. Synthasome's “X-Repair” medical device appears to be related to this patent and has been granted FDA 510(k) clearance by the US Food and Drug Administration (FDA), (http://www.synthasome.com/xRepair.php).
Another approach is described by Qiao et al., “Compositional and in Vitro Evaluation of Nonwoven Type I Collagen/Poly-dl-lactic Acid Scaffolds for Bone Regeneration,” Journal of Functional Biomaterials 2015, 6, 667-686; doi:10.3390/jfb6030667. This article describes electrospun blends of Poly-d,l-lactic acid (PDLLA) with type I collagen. Various blends are described with ratios of 40/60, 60/40 and 80/20 polymer blend by weight (PDLLA/Collagen). Qiao described a co-solvent system, and reported that chemical cross linking was essential to ensure long term stability of this material in cell culture. According to Qiao, scaffolds of PDLLA/collagen at a 60:40 weight ratio provided the greatest stability over a five-week culture period.
The use of constructs for muscle implants is also described by Lee et al., U.S. Pat. No. 9,421,305 (2016), “Aligned Scaffolding System for Skeletal Muscle Regeneration.” The patent discusses an anisotropic muscle implant made of electrospun fibers oriented along a longitudinal axis and cross linked to form a scaffold. Cells are seeded on the fibers to form myotubes. The fibers may be formed from natural polymers and/or synthetic polymers. Natural polymers include, for example, collagen, elastin, proteoglycans and hyaluronan. Synthetic polymers include, for example, polycaprolactone (PCL), poly(D-L-lactide-co-glycolide) (PLGA), polylactide (PLA), and poly(lactide-co-captrolactone) (PLCL). The fibers also may include hydrogels, microparticles, liposomes or vesicles. When blended, the ratio of natural polymer to synthetic polymer are between 2:1 and 1:2 by weight.
Electrospun scaffolds for generation of soft tissue replacements are described by Sensini et al., “Biofabrication of Bundles of Poly(lactic acid)-collagen Blends Mimicking the Fascicles of the Human Achilles Tendon,” Biofabrication 9 (2017) 015025, doi.org/10.1088/1758-5090/aa6204. Two different blends of PLLA and collagen were compared with bundles of pure collagen.
Yang et al., US Published Patent Application 2014/0011416 (2014), “Three Dimensionally and Randomly Oriented Fibrous Structures,” describes a method for producing randomly and evenly oriented three dimensional fibrous structures via electrospinning. It describes electrospinning a dope comprising one or more polymers, such as collagen, polylactic acid (PLA) and others, a solvent and a surfactant. The surfactant can be one or more of a diverse group including anionic surfactants, cationic surfactants, nonionic surfactants and zwitterionic surfactants. The spinning dope also includes one or more of a variety of solvents including acetic acid, chloroform, dimethyl sulfoxide (DMSO), ethanol, methanol and phosphate buffered saline.
And Dong et al., U.S. Pat. No. 8,318,903 (2012), “Benign Solvents for Forming Protein Structures,” describes methods for forming various protein structures by dissolving a protein, such as collagen, in a benign solvent comprising water, alcohol and salt. It also describes conventional electrospinning techniques.
Elamparithi et al., Indian published patent application IN640CHE2013 (2013), “A Method for Preparing a Three-Dimensional Collagen Fiber Mat Using Benign Solvent and Products Thereof,” describes a three dimensional, electrospun collagen mat prepared with a combination of acetic acid and DMSO as an environmentally benign solvent system. Another article by Elamparithi and colleagues uses the solvent system in a process of forming electrospun gelatin. See, for example, “Gelatin Electrospun Nanofibrous Matrices for Cardiac Tissue Engineering Applications,” International Journal of Polymeric Materials and Polymeric Biomaterials 66(1):20-27 (2017).